title: Chinese prescription kangen-karyu ameliorates the development of diabetic hepatic damages via regulating oxidative stress and inflammation in the liver of db/db mice.
abstract: The prevention and treatment of diabetic complications are considered to be the most important for the general care of diabetic patients. We have been conducting pre-clinical animal experiments related to diabetes using kangen-karyu, a Chinese prescription, to examine its therapeutic potential. In the present study, we further studied the anti-diabetic mechanism of kangen-karyu, especially on the regulation of hyperglycemia-induced hepatic oxidative stress and inflammation in db/db mice. Kangen-karyu (100 or 200 mg/kg body weight/day, per os (p.o.) was administered every day for 18 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. The administration of kangen-karyu decreased the elevated serum and hepatic glucose concentration in db/db mice. The elevated expressions of p22(phox) and Nox-4 proteins (reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits) were significantly decreased after kangen-karyu treatments. The oxidative stress-related markers in hepatic tissue (reactive oxygen species, reduced glutathione/oxidized glutathione ratio, and thiobarbituric acid-reactive substance) were also significantly ameliorated by the kangen-karyu treatments. The db/db mice exhibited the up-regulation of nuclear factor-κBp65, cyclooxygenase-2, and inducible nitric oxide synthase levels in the liver; however, kangen-karyu treatment significantly reduced those expressions. Taking these into consideration, our findings support the therapeutic evidence for kangen-karyu ameliorating the development of diabetic hepatic damages via regulating oxidative stress and inflammation.
authors.affiliation: Institute of Natural Medicine, University of Toyama, Sugitani, Toyama 930–0194, Japan.
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamabe
authors.forename: Takuya
authors.initials: T
authors.lastname: Okamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Toriizuka
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010080:Oxazoles / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy
chemical_list: C119678:4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; C468270:Kangen-karyu; D016328:NF-kappa B; D010080:Oxazoles; D052247:Nitric Oxide Synthase Type II; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D005947:Glucose